Chymase-containing mast cells in human arterial intima: implications for atherosclerotic disease.
Many of the mast cells present in human atherosclerotic lesions contain chymase. As the lesions progress to more severe forms, the number of such mast cells increases, and their activity (degree of degranulation) increases. Exocytosed heparin-bound chymase may be involved in the development of both early (fatty streaks) and late (thrombotic) atherosclerotic lesions. Experimental studies with rat serosal mast cells have revealed that chymase can degrade the apolipoprotein B-100 component of low-density lipoprotein (LDL) particles and the apolipoprotein A component of high-density lipoprotein (HDL) particles. Both of these chymase actions on apolipoproteins tend to increase the cholesterol content of macrophages and to convert them into the foam cells typical of early atherosclerotic lesions. In atheromatous plaques, the late atherosclerotic lesions, the chymase-containing mast cells may render the plaques unstable and their caps susceptible to rupture when chymase activates the interstitial procollagenase secreted by the macrophages in the plaque caps. Definition of the quantitative importance of chymase in the pathogenesis of atherosclerosis and its complications remains an exciting challenge for the future.
Kovanen
P T
PT
Wihuri Research Institute, Helsinki, Finland.
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000378:metabolism; D053818:Chymases; D018920:Coculture Techniques; D003324:Coronary Artery Disease / Q000503:physiopathology; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000737:chemistry / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000502:physiology*; D017539:Tunica Intima / Q000166:cytology*
D008078:Cholesterol, LDL; D012697:Serine Endopeptidases; D053818:Chymases